Enteral Acetaminophen Bioavailability in Pediatric Intensive Care Patients Determined With an Oral Microtracer and Pharmacokinetic Modeling to Optimize Dosing
Bibliographic record
Abstract
OBJECTIVES: Decreasing morbidity and mortality by rationalizing drug treatment in the critically ill is of paramount importance but challenging as the underlying clinical condition may lead to large variation in drug disposition and response. New microtracer methodology is now available to gain knowledge on drug disposition in the intensive care. On the basis of studies in healthy adults, physicians tend to assume that oral doses of acetaminophen will be completely absorbed and therefore prescribe the same dose per kilogram for oral and IV administration. As the oral bioavailability of acetaminophen in critically ill children is unknown, we designed a microtracer study to shed a light on this issue. DESIGN: An innovative microtracer study design with population pharmacokinetics. SETTING: A tertiary referral PICU. PATIENTS: Stable critically ill children, 0-6 years old, and already receiving IV acetaminophen. INTERVENTIONS: Concomitant administration of an oral C radiolabeled acetaminophen microtracer (3 ng/kg) with IV acetaminophen treatment (15 mg/kg every 6 hr). MEASUREMENTS: Blood was drawn from an indwelling arterial or central venous catheter up to 24 hours after C acetaminophen microtracer administration. Acetaminophen concentrations were measured by liquid chromatography-mass spectrometry and C concentrations by accelerated mass spectrometry. MAIN RESULTS: In 47 patients (median age of 6.1 mo; Q1-Q3, 1.8-20 mo) the mean enteral bioavailability was 72% (range, 11-91%). With a standard dose (15 mg/kg 4 times daily), therapeutic steady-state concentrations were 2.5 times more likely to be reached with IV than with oral administration. CONCLUSIONS: Microtracer studies present a new opportunity to gain knowledge on drug disposition in the intensive care. Using this modality in children in the pediatric intensive care, we showed that enteral administration of acetaminophen results in less predictable exposure and higher likelihood of subtherapeutic blood concentration than does IV administration. IV dosing may be preferable to ensure adequate pain relief.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".